A Study To Evaluate The Safety, Tolerability And Pharmacokinetics of HS-10345 In Treatment-Resistant Depression

NCT05196971 | Completed Phase 1

• 1 other identifier: HS-10345-102
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety, tolerability and pharmacokinetics of intranasal HS-10345 (84mg) compared with placebo in participants with treatment-resistant depression (TRD).

Conditions

Treatment Resistant Depressive Disorder

Keywords

Treatment resistant depressive disorder; Intranasal; HS-10345

Outcome Measures

Primary Outcomes (5)

• Number of participants with adverse events (AEs) and Serious Adverse Events (SAEs)

  Participants during hospitalization will be closely observed to assure maximal safety and to collect occurrence of all adverse event. To follow-up on the 7th day after discharge, all participants will return to the hospital for information regarding their health condition. All adverse events will be collected with special attention to occurrence of psychotomimetic and dissociative effects after study drug administration.

  up to 7 weeks

• Change from Baseline (Day -1) in Columbia-Suicide Severity Rating Scale (C-SSRS) Total Score at Day 15 in the Double-Blind Treatment Phase

  This scale is intended to be used by individuals who have received training in its administration. The questions contained in the Columbia-Suicide Severity Rating Scale are suggested probes. Ultimately, the determination of the presence of suicidal ideation or behavior depends on the judgment of the individual administering the scale. A negative change in score indicates improvement.

  up to 15 days

• Change from Baseline (Day -1) in The Clinician Administered Dissociative States Scale (CADSS) Total Score at 40 minutes and 2 hours after dosing in the Double-Blind Treatment Phase- ANCOVA Analysis on Ranks

  This scale is intended to be used to assess the dissociative states of participants. It contains 23 objective items, every item ranges from 0 to 4. A negative change in score indicates improvement.

  up to 2 hours

• Change From pre-dosing in Modified Observer's Assessment of Alertness and Sedation (MOAA/S) Total Score at 20 minutes、40 minutes and 2 hours after dosing in the Double-Blind Treatment Phase- ANCOVA Analysis on Ranks

  The Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scale is frequently used in sedation-related drug and device studies to assess a subject's level of sedation. It ranges from 0 to 5, with a score of 5 defined as awake or minimally sedated, and a score of 0 defined as general anesthesia. This scale is intended to be used by individuals who have received training in its administration. A positive change in score indicates improvement.

  up to 2 hours

• Change from Baseline (Day -1) in Physician Withdrawal Checklist (PWC-20) Total Score at Day 15 in the Double-Blind Treatment Phase and Day 21 in the Follow-Up Phase- ANCOVA Analysis on Ranks

  The PWC-20 was developed to detect any potential BZ-like treatment discontinuation (withdrawal) symptoms caused by experimental anxiolytics of the non-SSRI type. A negative change in score indicates improvement.

  up to 15 days

Secondary Outcomes (6)

• Cmax - maximum HS-10345 plasma concentration

  up to 72 hours after each study drug administration

• AUC (0-24) - area under the HS-10345 plasma concentration-time curve from time 0 to 24 hours after study drug administration

  up to 24 hours after each study drug administration

• Tmax - time to reach maximum HS-10345 plasma concentration

  up to 72 hours after each study drug administration

• AUC (0-inf) - area under the HS-10345 plasma concentration-time curve from time 0 to infinity time

  up to 72 hours after each study drug administration

• T1/2 - plasma elimination half-life for HS-10345

  up to 72 hours after each study drug administration

Study Arms (2)

HS-10345 84mg

EXPERIMENTAL

Participants will self-administer intranasal HS-10345 84mg on Days 1, 4, 8, and 11 during the double-blind phase

Drug: HS-10345 84mg

Placebo

PLACEBO COMPARATOR

Participants will be self-administered on Days 1, 4, 8, and 11 during the double-blind phase

Drug: Placebo

Interventions

HS-10345 84mg DRUG

6 sprays of HS-10345 84 mg self-administered as an intranasal formulation for 4 days (Days 1, 4, 8, 11) during the double-blind phase

Also known as: HS-10345

HS-10345 84mg

Placebo DRUG

6 sprays of placebo self-administered as an intranasal formulation for 4 days (Days 1, 4, 8, 11) during the double-blind phase

Also known as: HS-10345 Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study.
• Participant must meet Diagnostic and Statistical Manual of Mental Disorders -5 Edition -Text Revised (DSM-5) diagnostic criteria for Major Depressive Disorder (MDD), without psychotic features, based upon clinical assessment, and confirmed by the Mini International Neuropsychiatric Interview (MINI).
• Participant must have had an inadequate response to at least 1 antidepressants in the current episode of depression assessed by the antidepressant treatment response questionnaire (ATRQ), and was taking another oral antidepressant 2 weeks before entering the screening period which will be assessed "non-response" by Montgomery Asberg Depression Rating Scale (MADRS) during the screening period, defined as MADRS total score reduced ≤25%.
• Comfortable with self-administration of intranasal medication and able to follow instructions provided.
• A woman of childbearing potential must have a negative serum (β-human chorionic gonadotropin \[β-hCG\]) at Screening and a negative urine pregnancy test prior to Period 1 randomization on Day 1.

You may not qualify if:

• Subject has a current DSM-5 diagnosis of psychotic disorder, MDD with psychosis, bipolar, obsessive compulsive disorder (OCD), intellectual disability, Autism spectrum Disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, and narcissistic personality disorder.
• Subject has suicidal ideation with intent to act within the past 6 months based on the Columbia-Suicide Severity Rating Scale (C-SSRS), or has a history of suicidal behavior within the past year as assessed on the C-SSRS.
• Subject has uncontrolled hypertension (SBP \> 140 mmHg or DBP \> 90 mmHg) despite diet, exercise or a stable dose of a permitted anti-hypertensive treatment at Screening or Day 1 prior to Period 1 randomization; or any past history of hypertensive crisis.
• Subject had a history of severe pulmonary insufficiency or SpO2\<93% at screening time or prior to dosing.
• Anatomical or medical conditions that may impede delivery or absorption of study medication.
• Subject is a woman who is pregnant, breast-feeding, or planning to become pregnant while enrolled in this study or within 12 weeks after the last dose of study drug.
• Hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody and human immunodeficiency virus (HIV) antibody tests positive.
• Subject has had major surgery, (e.g., requiring general anesthesia) within 12 weeks before screening, or has surgery planned during the time the subject is expected to participate in the study.

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Beijing Anding Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Gang Wang

  Beijing Anding Hospital, Capital Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2022
• First Posted: January 19, 2022
• Study Start: October 28, 2021
• Primary Completion: April 30, 2022
• Study Completion: October 31, 2022
• Last Updated: March 9, 2023

Record last verified: 2023-02

Locations

CN (1)